Free Standard AU & NZ Shipping For All Book Orders Over $80!
Register      Login
Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
REVIEW (Open Access)

Current status of embryo models created from pluripotent stem cells

Maria Carolina Zimara A , Toshihiko Ezashi A and Ye Yuan https://orcid.org/0000-0002-9995-2209 A *
+ Author Affiliations
- Author Affiliations

A Colorado Center for Reproductive Medicine, 10290 RidgeGate Circle, Lone Tree, CO 80124, USA.

* Correspondence to: yyuan@ccrmivf.com

Reproduction, Fertility and Development 37, RD24138 https://doi.org/10.1071/RD24138

© 2025 The Author(s) (or their employer(s)). Published by CSIRO Publishing on behalf of the IETS. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND)

Abstract

The mystery of genesis has fascinated human inquiry ever since Aristotle in the 4th century BCE and likely even earlier. Observations of carcinomas in the last century led to the derivation of embryonic stem cells and induced pluripotent stem cells. These remarkable cells recently allowed scientists to develop embryo models that emulate the natural developmental behavior of embryos. In this review, we present how this line of research is unfolding, and discuss its applications in human in vitro fertilization, regenerative medicine, animal reproduction and conservation. As we navigate this frontier, human genesis continues to inspire and challenge, shaping our understanding of life’s fundamental processes and opening doors to unprecedented applications of stem cell technologies.

Keywords: agriculture animal, blastoids, developmental biology, embryo models, embryogenesis, embryoids, gastrulation, human IVF, peri-implantation development, pluripotent stem cells, pre-implantation development, regenerative medicine.

References

Aguilera-Castrejon A, Oldak B, Shani T, Ghanem N, Itzkovich C, Slomovich S, Tarazi S, Bayerl J, Chugaeva V, Ayyash M, Ashouokhi S, Sheban D, Livnat N, Lasman L, Viukov S, Zerbib M, Addadi Y, Rais Y, Cheng S, Stelzer Y, Keren-Shaul H, Shlomo R, Massarwa R, Novershtern N, Maza I, Hanna JH (2021) Ex utero mouse embryogenesis from pre-gastrulation to late organogenesis. Nature 593(7857), 119-124.
| Crossref | Google Scholar | PubMed |

Ai Z, Niu B, Yin Y, Xiang L, Shi G, Duan K, Wang S, Hu Y, Zhang C, Zhang C, Rong L, Kong R, Chen T, Guo Y, Liu W, Li N, Zhao S, Zhu X, Mai X, Li Y, Wu Z, Zheng Y, Fu J, Ji W, Li T (2023) Dissecting peri-implantation development using cultured human embryos and embryo-like assembloids. Cell Research 33(9), 661-678.
| Crossref | Google Scholar | PubMed |

Amadei G, Handford CE, Qiu C, De Jonghe J, Greenfeld H, Tran M, Martin BK, Chen DY, Aguilera-Castrejon A, Hanna JH, Elowitz MB, Hollfelder F, Shendure J, Glover DM, Zernicka-Goetz M (2022) Embryo model completes gastrulation to neurulation and organogenesis. Nature 610(7930), 143-153.
| Crossref | Google Scholar | PubMed |

Appleton E, Hong K, Rodríguez-Caycedo C, Tanaka Y, Ashkenazy-Titelman A, Bhide K, Rasmussen-Ivey C, Ambriz-Peña X, Korover N, Bai H, Quieroz A, Nelson J, Rathod G, Knox G, Morgan M, Malviya N, Zhang K, McNutt B, Kehler J, Kowalczyk A, Bow A, McLendon B, Cantarel B, James M, Mason CE, Gray C, Koehler KR, Pearson V, Lamm B, Church G, Hysolli E (2024) Derivation of elephant induced pluripotent stem cells. bioRxiv
| Crossref | Google Scholar |

Arias AM, Marikawa Y, Moris N (2022) Gastruloids: Pluripotent stem cell models of mammalian gastrulation and embryo engineering. Developmental Biology 488, 35-46.
| Crossref | Google Scholar |

Bayerl J, Ayyash M, Shani T, Manor YS, Gafni O, Massarwa R, Kalma Y, Aguilera-Castrejon A, Zerbib M, Amir H, Sheban D, Geula S, Mor N, Weinberger L, Naveh Tassa S, Krupalnik V, Oldak B, Livnat N, Tarazi S, Tawil S, Wildschutz E, Ashouokhi S, Lasman L, Rotter V, Hanna S, Ben-Yosef D, Novershtern N, Viukov S, Hanna JH (2021) Principles of signaling pathway modulation for enhancing human naïve pluripotency induction. Cell Stem Cell 28(9), 1549-1565.e12.
| Crossref | Google Scholar |

Bedzhov I, Zernicka-Goetz M (2014) Self-organizing properties of mouse pluripotent cells initiate morphogenesis upon implantation. Cell 156(5), 1032-1044.
| Crossref | Google Scholar | PubMed |

Bogliotti YS, Wu J, Vilarino M, Okamura D, Soto DA, Zhong C, Sakurai M, Sampaio RV, Suzuki K, Izpisua Belmonte JC, Ross PJ (2018) Efficient derivation of stable primed pluripotent embryonic stem cells from bovine blastocysts. Proceedings of the National Academy of Sciences of the United States of America 115(9), 2090-2095.
| Crossref | Google Scholar |

Coucouvanis E, Martin GR (1995) Signals for death and survival: a two-step mechanism for cavitation in the vertebrate embryo. Cell 83(2), 279-287.
| Crossref | Google Scholar | PubMed |

Deglincerti A, Croft GF, Pietila LN, Zernicka-Goetz M, Siggia ED, Brivanlou AH (2016) Self-organization of the in vitro attached human embryo. Nature 533(7602), 251-254.
| Crossref | Google Scholar | PubMed |

Etoc F, Metzger J, Ruzo A, Kirst C, Yoney A, Ozair MZ, Brivanlou AH, Siggia ED (2016) A balance between secreted inhibitors and edge sensing controls gastruloid self-organization. Developmental Cell 39(3), 302-315.
| Crossref | Google Scholar | PubMed |

Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292(5819), 154-156.
| Crossref | Google Scholar | PubMed |

Ezashi T, Yuan Y, Roberts RM (2016) Pluripotent stem cells from domesticated mammals. Annual Review of Animal Biosciences 4, 223-253.
| Crossref | Google Scholar | PubMed |

Gafni O, Weinberger L, Mansour AAF, Manor YS, Chomsky E, Ben-Yosef D, Kalma Y, Viukov S, Maza I, Zviran A, Rais Y, Shipony Z, Mukamel Z, Krupalnik V, Zerbib M, Geula S, Caspi I, Schneir D, Shwartz T, Gilad S, Amann-Zalcenstein D, Benjamin S, Amit I, Tanay A, Massarwa R, Novershtern N, Hanna JH (2013) Derivation of novel human ground state naive pluripotent stem cells. Nature 504(7479), 282-286.
| Crossref | Google Scholar | PubMed |

Gao X, Nowak-Imialek M, Chen X, Chen D, Herrmann D, Ruan D, Chen ACH, Eckersley-Maslin MA, Ahmad S, Lee YL, Kobayashi T, Ryan D, Zhong J, Zhu J, Wu J, Lan G, Petkov S, Yang J, Antunes L, Campos LS, Fu B, Wang S, Yong Y, Wang X, Xue SG, Ge L, Liu Z, Huang Y, Nie T, Li P, Wu D, Pei D, Zhang Y, Lu L, Yang F, Kimber SJ, Reik W, Zou X, Shang Z, Lai L, Surani A, Tam PPL, Ahmed A, Yeung WSB, Teichmann SA, Niemann H, Liu P (2019) Establishment of porcine and human expanded potential stem cells. Nature Cell Biology 21(6), 687-699.
| Crossref | Google Scholar | PubMed |

Gardner RL, Papaioannou VE (1975) Differentiation in the trophectoderm and inner cell mass. In ‘The early development of mammals’. (Eds M Balls, AE Wild) pp. 107–132. (Cambridge University Press: London, UK)

Goszczynski DE, Cheng H, Demyda-Peyrás S, Medrano JF, Wu J, Ross PJ (2019) In vitro breeding: application of embryonic stem cells to animal production. Biology of Reproduction 100(4), 885-895.
| Crossref | Google Scholar | PubMed |

Harrison SE, Sozen B, Christodoulou N, Kyprianou C, Zernicka-Goetz M (2017) Assembly of embryonic and extraembryonic stem cells to mimic embryogenesis in vitro. Science 356(6334), eaal1810.
| Crossref | Google Scholar |

Heemskerk I, Warmflash A (2016) Pluripotent stem cells as a model for embryonic patterning: From signaling dynamics to spatial organization in a dish. Developmental Dynamics 245(10), 976-990.
| Crossref | Google Scholar | PubMed |

Heidari Khoei H, Javali A, Kagawa H, Sommer TM, Sestini G, David L, Slovakova J, Novatchkova M, Scholte Op Reimer Y, Rivron N (2023) Generating human blastoids modeling blastocyst-stage embryos and implantation. Nature Protocols 18(5), 1584-1620.
| Crossref | Google Scholar | PubMed |

Hertig AT, Rock J, Adams EC (1956) A description of 34 human ova within the first 17 days of development. American Journal of Anatomy 98(3), 435-493.
| Crossref | Google Scholar | PubMed |

Hikabe O, Hamazaki N, Nagamatsu G, Obata Y, Hirao Y, Hamada N, Shimamoto S, Imamura T, Nakashima K, Saitou M, Hayashi K (2016) Reconstitution in vitro of the entire cycle of the mouse female germ line. Nature 539(7628), 299-303.
| Crossref | Google Scholar | PubMed |

Hildebrandt TB, Hermes R, Colleoni S, Diecke S, Holtze S, Renfree MB, Stejskal J, Hayashi K, Drukker M, Loi P, Göritz F, Lazzari G, Galli C (2018) Embryos and embryonic stem cells from the white rhinoceros. Nature Communications 9(1), 2589.
| Crossref | Google Scholar | PubMed |

Hislop J, Song Q, Keshavarz FK, Alavi A, Schoenberger R, LeGraw R, Velazquez JJ, Mokhtari T, Taheri MN, Rytel M, Chuva de Sousa Lopes SM, Watkins S, Stolz D, Kiani S, Sozen B, Bar-Joseph Z, Ebrahimkhani MR (2024) Modelling post-implantation human development to yolk sac blood emergence. Nature 626(7998), 367-376.
| Crossref | Google Scholar | PubMed |

Hou Z, An L, Han J, Yuan Y, Chen D, Tian J (2018) Revolutionize livestock breeding in the future: an animal embryo-stem cell breeding system in a dish. Journal of Animal Science and Biotechnology 9, 1-11.
| Crossref | Google Scholar |

Jannaman EA, Liu K, Schoolcraft WB, Yuan Y (2023) Optimization of embryo vitrification media using stem cell derived human blastoids. Fertility and Sterility 120(4), e67-e68.
| Crossref | Google Scholar |

Kagawa H, Javali A, Khoei HH, Sommer TM, Sestini G, Novatchkova M, Scholte Op Reimer Y, Castel G, Bruneau A, Maenhoudt N, Lammers J, Loubersac S, Freour T, Vankelecom H, David L, Rivron N (2022) Human blastoids model blastocyst development and implantation. Nature 601(7894), 600-605.
| Crossref | Google Scholar | PubMed |

Karvas RM, Zemke JE, Ali SS, Upton E, Sane E, Fischer LA, Dong C, Park KM, Wang F, Park K, Hao S, Chew B, Meyer B, Zhou C, Dietmann S, Theunissen TW (2023) 3D-cultured blastoids model human embryogenesis from pre-implantation to early gastrulation stages. Cell Stem Cell 30(9), 1148-1165.e7.
| Crossref | Google Scholar |

Kime C, Kiyonari H, Ohtsuka S, Kohbayashi E, Asahi M, Yamanaka S, Takahashi M, Tomoda K (2019) Induced 2C expression and implantation-competent blastocyst-like cysts from primed pluripotent stem cells. Stem Cell Reports 13(3), 485-498.
| Crossref | Google Scholar | PubMed |

Lau KYC, Rubinstein H, Gantner CW, Hadas R, Amadei G, Stelzer Y, Zernicka-Goetz M (2022) Mouse embryo model derived exclusively from embryonic stem cells undergoes neurulation and heart development. Cell Stem Cell 29(10), 1445-1458.e8.
| Crossref | Google Scholar |

Li R, Zhong C, Yu Y, Liu H, Sakurai M, Yu L, Min Z, Shi L, Wei Y, Takahashi Y, Liao HK, Qiao J, Deng H, Nuñez-Delicado E, Rodriguez Esteban C, Wu J, Izpisua Belmonte JC (2019) Generation of blastocyst-like structures from mouse embryonic and adult cell cultures. Cell 179(3), 687-702.e18.
| Crossref | Google Scholar |

Linneberg-Agerholm M, Wong YF, Romero Herrera JA, Monteiro RS, Anderson KGV, Brickman JM (2019) Naïve human pluripotent stem cells respond to Wnt, Nodal and LIF signalling to produce expandable naïve extra-embryonic endoderm. Development 146(24), dev180620.
| Crossref | Google Scholar |

Liu X, Tan JP, Schröder J, Aberkane A, Ouyang JF, Mohenska M, Lim SM, Sun YBY, Chen J, Sun G, Zhou Y, Poppe D, Lister R, Clark AT, Rackham OJL, Zenker J, Polo JM (2021) Modelling human blastocysts by reprogramming fibroblasts into iBlastoids. Nature 591(7851), 627-632.
| Crossref | Google Scholar | PubMed |

Liu L, Oura S, Markham Z, Hamilton JN, Skory RM, Li L, Sakurai M, Wang L, Pinzon-Arteaga CA, Plachta N, Hon GC, Wu J (2023) Modeling post-implantation stages of human development into early organogenesis with stem-cell-derived peri-gastruloids. Cell 186(18), 3776-3792.e16.
| Crossref | Google Scholar |

Logsdon DM, Ezashi T, Yu L, Schoolcraft WB, Katz-Jaffe M, Wu J, Yuan Y (2022) Optimizing extended culture conditions of stem cell derived blastoids to mimic human implantation in vitro. Fertility and Sterility 118(4), e37.
| Crossref | Google Scholar |

Lv B, An Q, Zeng Q, Zhang X, Lu P, Wang Y, Zhu X, Ji Y, Fan G, Xue Z (2019) Single-cell RNA sequencing reveals regulatory mechanism for trophoblast cell-fate divergence in human peri-implantation conceptuses. PLOS Biology 17(10), e3000187.
| Crossref | Google Scholar |

Ma H, Zhai J, Wan H, Jiang X, Wang X, Wang L, Xiang Y, He X, Zhao ZA, Zhao B, Zheng P, Li L, Wang H (2019) In vitro culture of cynomolgus monkey embryos beyond early gastrulation. Science 366(6467), eaax7890.
| Crossref | Google Scholar |

Martin GR (1975) Teratocarcinomas as a model system for the study of embryogenesis and neoplasia. Cell 5(3), 229-243.
| Crossref | Google Scholar | PubMed |

Mazid MA, Ward C, Luo Z, Liu C, Li Y, Lai Y, Wu L, Li J, Jia W, Jiang Y, Liu H, Fu L, Yang Y, Ibañez DP, Lai J, Wei X, An J, Guo P, Yuan Y, Deng Q, Wang Y, Liu Y, Gao F, Wang J, Zaman S, Qin B, Wu G, Maxwell PH, Xu X, Liu L, Li W, Esteban MA (2022) Rolling back human pluripotent stem cells to an eight-cell embryo-like stage. Nature 605(7909), 315-324.
| Crossref | Google Scholar | PubMed |

Niu Y, Sun N, Li C, Lei Y, Huang Z, Wu J, Si C, Dai X, Liu C, Wei J, Liu L, Feng S, Kang Y, Si W, Wang H, Zhang E, Zhao L, Li Z, Luo X, Cui G, Peng G, Izpisúa Belmonte JC, Ji W, Tan T (2019) Dissecting primate early post-implantation development using long-term in vitro embryo culture. Science 366(6467), eaaw5754.
| Crossref | Google Scholar |

Okae H, Toh H, Sato T, Hiura H, Takahashi S, Shirane K, Kabayama Y, Suyama M, Sasaki H, Arima T (2018) Derivation of human trophoblast stem cells. Cell Stem Cell 22(1), 50-63.e6.
| Crossref | Google Scholar | PubMed |

Okubo T, Rivron N, Kabata M, Masaki H, Kishimoto K, Semi K, Nakajima-Koyama M, Kunitomi H, Kaswandy B, Sato H, Nakauchi H, Woltjen K, Saitou M, Sasaki E, Yamamoto T, Takashima Y (2024) Hypoblast from human pluripotent stem cells regulates epiblast development. Nature 626(7998), 357-366.
| Crossref | Google Scholar | PubMed |

Oldak B, Wildschutz E, Bondarenko V, Comar MY, Zhao C, Aguilera-Castrejon A, Tarazi S, Viukov S, Pham TXA, Ashouokhi S, Lokshtanov D, Roncato F, Ariel E, Rose M, Livnat N, Shani T, Joubran C, Cohen R, Addadi Y, Chemla M, Kedmi M, Keren-Shaul H, Pasque V, Petropoulos S, Lanner F, Novershtern N, Hanna JH (2023) Complete human day 14 post-implantation embryo models from naive ES cells. Nature 622(7983), 562-573.
| Crossref | Google Scholar | PubMed |

O’Rahilly R, Müller F (1987) Developmental stages in human embryos. Carnegie Institution of Washington. Available at https://www.ehd.org/developmental-stages/stage0.php

Pedroza M, Gassaloglu SI, Dias N, Zhong L, Hou TCJ, Kretzmer H, Smith ZD, Sozen B (2023) Self-patterning of human stem cells into post-implantation lineages. Nature 622(7983), 574-583.
| Crossref | Google Scholar | PubMed |

Peerani R, Rao BM, Bauwens C, Yin T, Wood GA, Nagy A, Kumacheva E, Zandstra PW (2007) Niche-mediated control of human embryonic stem cell self-renewal and differentiation. The EMBO Journal 26(22), 4744-4755.
| Crossref | Google Scholar | PubMed |

Peyron A, Limousin H, Lafay B (1936) Sur quelques notions fondamentales, dans l’étude des embryomes. Facteurs d’organisation et polyembryonie. Bulletin de l’Association Française pour l’Étude du Cancer 25, 850-873 [In French].
| Google Scholar |

Pinzón-Arteaga CA, Wang Y, Wei Y, Ribeiro Orsi AE, Li L, Scatolin G, Liu L, Sakurai M, Ye J, Ming H, Yu L, Li B, Jiang Z, Wu J (2023) Bovine blastocyst-like structures derived from stem cell cultures. Cell Stem Cell 30(5), 611-616.e7.
| Crossref | Google Scholar |

Red-Horse K, Zhou Y, Genbacev O, Prakobphol A, Foulk R, McMaster M, Fisher SJ (2004) Trophoblast differentiation during embryo implantation and formation of the maternal-fetal interface. Journal of Clinical Investigation 114(6), 744-754.
| Crossref | Google Scholar | PubMed |

Rivron NC, Frias-Aldeguer J, Vrij EJ, Boisset JC, Korving J, Vivié J, Truckenmüller RK, van Oudenaarden A, van Blitterswijk CA, Geijsen N (2018) Blastocyst-like structures generated solely from stem cells. Nature 557(7703), 106-111.
| Crossref | Google Scholar | PubMed |

Rossant J, Cross JC (2001) Placental development: lessons from mouse mutants. Nature Reviews Genetics 2(7), 538-548.
| Crossref | Google Scholar | PubMed |

Schuldiner M, Yanuka O, Itskovitz-Eldor J, Melton DA, Benvenisty N (2000) Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America 97(21), 11307-11312.
| Crossref | Google Scholar |

Shahbazi MN, Jedrusik A, Vuoristo S, Recher G, Hupalowska A, Bolton V, Fogarty NME, Campbell A, Devito L, Ilic D, Khalaf Y, Niakan KK, Fishel S, Zernicka-Goetz M (2016) Self-organization of the human embryo in the absence of maternal tissues. Nature Cell Biology 18(6), 700-708.
| Crossref | Google Scholar | PubMed |

Shao Y, Taniguchi K, Townshend RF, Miki T, Gumucio DL, Fu J (2017) A pluripotent stem cell-based model for post-implantation human amniotic sac development. Nature Communications 8(1), 208.
| Crossref | Google Scholar | PubMed |

Simunovic M, Metzger JJ, Etoc F, Yoney A, Ruzo A, Martyn I, Croft G, You DS, Brivanlou AH, Siggia ED (2019) A 3D model of a human epiblast reveals BMP4-driven symmetry breaking. Nature Cell Biology 21(7), 900-910.
| Crossref | Google Scholar | PubMed |

Simunovic M, Siggia ED, Brivanlou AH (2022) In vitro attachment and symmetry breaking of a human embryo model assembled from primed embryonic stem cells. Cell Stem Cell 29(6), 962-972.e4.
| Crossref | Google Scholar |

Sozen B, Amadei G, Cox A, Wang R, Na E, Czukiewska S, Chappell L, Voet T, Michel G, Jing N, Glover DM, Zernicka-Goetz M (2018) Self-assembly of embryonic and two extra-embryonic stem cell types into gastrulating embryo-like structures. Nature Cell Biology 20(8), 979-989.
| Crossref | Google Scholar | PubMed |

Sozen B, Cox AL, De Jonghe J, Bao M, Hollfelder F, Glover DM, Zernicka-Goetz M (2019) Self-organization of mouse stem cells into an extended potential blastoid. Developmental Cell 51(6), 698-712.e8.
| Crossref | Google Scholar |

Stevens LC (1967) The biology of teratomas. Advances in Morphogenesis 6, 1-31.
| Crossref | Google Scholar | PubMed |

Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4), 663-676.
| Crossref | Google Scholar | PubMed |

Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5), 861-872.
| Crossref | Google Scholar | PubMed |

Takashima Y, Guo G, Loos R, Nichols J, Ficz G, Krueger F, Oxley D, Santos F, Clarke J, Mansfield W, Reik W, Bertone P, Smith A (2014) Resetting transcription factor control circuitry toward ground-state pluripotency in human. Cell 158(6), 1254-1269.
| Crossref | Google Scholar | PubMed |

Tarazi S, Aguilera-Castrejon A, Joubran C, Ghanem N, Ashouokhi S, Roncato F, Wildschutz E, Haddad M, Oldak B, Gomez-Cesar E, Livnat N, Viukov S, Lokshtanov D, Naveh-Tassa S, Rose M, Hanna S, Raanan C, Brenner O, Kedmi M, Keren-Shaul H, Lapidot T, Maza I, Novershtern N, Hanna JH (2022) Post-gastrulation synthetic embryos generated ex utero from mouse naïve ESCs. Cell 185(18), 3290-3306.e25.
| Crossref | Google Scholar |

Taubenschmid-Stowers J, Rostovskaya M, Santos F, Ljung S, Argelaguet R, Krueger F, Nichols J, Reik W (2022) 8C-like cells capture the human zygotic genome activation program in vitro. Cell Stem Cell 29(3), 449-459.e6.
| Crossref | Google Scholar |

ten Berge D, Koole W, Fuerer C, Fish M, Eroglu E, Nusse R (2008) Wnt signaling mediates self-organization and axis formation in embryoid bodies. Cell Stem Cell 3(5), 508-518.
| Crossref | Google Scholar | PubMed |

Theunissen TW, Powell BE, Wang H, Mitalipova M, Faddah DA, Reddy J, Fan ZP, Maetzel D, Ganz K, Shi L, Lungjangwa T, Imsoonthornruksa S, Stelzer Y, Rangarajan S, D’Alessio A, Zhang J, Gao Q, Dawlaty MM, Young RA, Gray NS, Jaenisch R (2014) Systematic identification of culture conditions for induction and maintenance of naïve human pluripotency. Cell Stem Cell 15(4), 471-487.
| Crossref | Google Scholar | PubMed |

Thomson JA, Kalishman J, Golos TG, Durning M, Harris CP, Becker RA, Hearn JP (1995) Isolation of a primate embryonic stem cell line. Proceedings of the National Academy of Sciences of the United States of America 92(17), 7844-7848.
| Crossref | Google Scholar |

Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282(5391), 1145-1147.
| Crossref | Google Scholar | PubMed |

van den Brink SC, Baillie-Johnson P, Balayo T, Hadjantonakis AK, Nowotschin S, Turner DA, Martinez Arias A (2014) Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells. Development 141(22), 4231-4242.
| Crossref | Google Scholar | PubMed |

Vrij EJ, Scholte Op Reimer YS, Roa Fuentes L, Misteli Guerreiro I, Holzmann V, Frias Aldeguer J, Sestini G, Koo BK, Kind J, van Blitterswijk CA, Rivron NC (2022) A pendulum of induction between the epiblast and extra-embryonic endoderm supports post-implantation progression. Development 149(20), dev192310.
| Crossref | Google Scholar |

Wang Y, Ming H, Yu L, Li J, Zhu L, Sun HX, Pinzon-Arteaga CA, Wu J, Jiang Z (2023) Establishment of bovine trophoblast stem cells. Cell Reports 42(5), 112439.
| Crossref | Google Scholar | PubMed |

Ware CB, Nelson AM, Mecham B, Hesson J, Zhou W, Jonlin EC, Jimenez-Caliani AJ, Deng X, Cavanaugh C, Cook S, Tesar PJ, Okada J, Margaretha L, Sperber H, Choi M, Blau CA, Treuting PM, Hawkins RD, Cirulli V, Ruohola-Baker H (2014) Derivation of naive human embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America 111(12), 4484-4489.
| Crossref | Google Scholar |

Warmflash A, Sorre B, Etoc F, Siggia ED, Brivanlou AH (2014) A method to recapitulate early embryonic spatial patterning in human embryonic stem cells. Nature Methods 11(8), 847-854.
| Crossref | Google Scholar | PubMed |

Weatherbee BAT, Gantner CW, Iwamoto-Stohl LK, Daza RM, Hamazaki N, Shendure J, Zernicka-Goetz M (2023) Pluripotent stem cell-derived model of the post-implantation human embryo. Nature 622(7983), 584-593.
| Crossref | Google Scholar | PubMed |

West RC, Ming H, Logsdon DM, Sun J, Rajput SK, Kile RA, Schoolcraft WB, Roberts RM, Krisher RL, Jiang Z, Yuan Y (2019) Dynamics of trophoblast differentiation in peri-implantation–stage human embryos. Proceedings of the National Academy of Sciences of the United States of America 116(45), 22635-22644.
| Crossref | Google Scholar |

Wu J, Fu J (2024) Toward developing human organs via embryo models and chimeras. Cell 187(13), 3194-3219.
| Crossref | Google Scholar | PubMed |

Wu J, Izpisua Belmonte JC (2015) Dynamic pluripotent stem cell states and their applications. Cell Stem Cell 17(5), 509-525.
| Crossref | Google Scholar | PubMed |

Xiang L, Yin Y, Zheng Y, Ma Y, Li Y, Zhao Z, Guo J, Ai Z, Niu Y, Duan K, He J, Ren S, Wu D, Bai Y, Shang Z, Dai X, Ji W, Li T (2020) A developmental landscape of 3D-cultured human pre-gastrulation embryos. Nature 577(7791), 537-542.
| Crossref | Google Scholar | PubMed |

Xu Y, Zhao J, Ren Y, Wang X, Lyu Y, Xie B, Sun Y, Yuan X, Liu H, Yang W, Fu Y, Yu Y, Liu Y, Mu R, Li C, Xu J, Deng H (2022) Derivation of totipotent-like stem cells with blastocyst-like structure forming potential. Cell Research 32(6), 513-529.
| Crossref | Google Scholar | PubMed |

Yamashiro C, Sasaki K, Yabuta Y, Kojima Y, Nakamura T, Okamoto I, Yokobayashi S, Murase Y, Ishikura Y, Shirane K, Sasaki H, Yamamoto T, Saitou M (2018) Generation of human oogonia from induced pluripotent stem cells in vitro. Science 362(6412), 356-360.
| Crossref | Google Scholar |

Yang J, Ryan DJ, Wang W, Tsang JCH, Lan G, Masaki H, Gao X, Antunes L, Yu Y, Zhu Z, Wang J, Kolodziejczyk AA, Campos LS, Wang C, Yang F, Zhong Z, Fu B, Eckersley-Maslin MA, Woods M, Tanaka Y, Chen X, Wilkinson AC, Bussell J, White J, Ramirez-Solis R, Reik W, Göttgens B, Teichmann SA, Tam PPL, Nakauchi H, Zou X, Lu L, Liu P (2017a) Establishment of mouse expanded potential stem cells. Nature 550(7676), 393-397.
| Crossref | Google Scholar | PubMed |

Yang Y, Liu B, Xu J, Wang J, Wu J, Shi C, Xu Y, Dong J, Wang C, Lai W, Zhu J, Xiong L, Zhu D, Li X, Yang W, Yamauchi T, Sugawara A, Li Z, Sun F, Li X, Li C, He A, Du Y, Wang T, Zhao C, Li H, Chi X, Zhang H, Liu Y, Li C, Duo S, Yin M, Shen H, Belmonte JCI, Deng H (2017b) Derivation of pluripotent stem cells with in vivo embryonic and extraembryonic potency. Cell 169(2), 243-257.e25.
| Crossref | Google Scholar |

Yang M, Yu H, Yu X, Liang S, Hu Y, Luo Y, Izsvák Z, Sun C, Wang J (2022) Chemical-induced chromatin remodeling reprograms mouse ESCs to totipotent-like stem cells. Cell Stem Cell 29(3), 400-418.e13.
| Crossref | Google Scholar |

Yoshimatsu S, Nakajima M, Iguchi A, Sanosaka T, Sato T, Nakamura M, Nakajima R, Arai E, Ishikawa M, Imaizumi K, Watanabe H, Okahara J, Noce T, Takeda Y, Sasaki E, Behr R, Edamura K, Shiozawa S, Okano H (2021) Non-viral induction of transgene-free iPSCs from somatic fibroblasts of multiple mammalian species. Stem Cell Reports 16(4), 754-770.
| Crossref | Google Scholar | PubMed |

Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318(5858), 1917-1920.
| Crossref | Google Scholar | PubMed |

Yu L, Wei Y, Duan J, Schmitz DA, Sakurai M, Wang L, Wang K, Zhao S, Hon GC, Wu J (2021a) Blastocyst-like structures generated from human pluripotent stem cells. Nature 591(7851), 620-626.
| Crossref | Google Scholar | PubMed |

Yu L, Wei Y, Sun HX, Mahdi AK, Pinzon Arteaga CA, Sakurai M, Schmitz DA, Zheng C, Ballard ED, Li J, Tanaka N, Kohara A, Okamura D, Mutto AA, Gu Y, Ross PJ, Wu J (2021b) Derivation of intermediate pluripotent stem cells amenable to primordial germ cell specification. Cell Stem Cell 28(3), 550-567.e12.
| Crossref | Google Scholar |

Yu X, Liang S, Chen M, Yu H, Li R, Qu Y, Kong X, Guo R, Zheng R, Izsvák Z, Sun C, Yang M, Wang J (2022) Recapitulating early human development with 8C-like cells. Cell Reports 39(12), 110994.
| Crossref | Google Scholar |

Yu L, Logsdon D, Pinzon-Arteaga CA, Duan J, Ezashi T, Wei Y, Ribeiro Orsi AE, Oura S, Liu L, Wang L, Liu K, Ding X, Zhan L, Zhang J, Nahar A, Stobbe C, Katz-Jaffe M, Schoolcraft WB, Tan T, Hon GC, Yuan Y, Wu J (2023) Large-scale production of human blastoids amenable to modeling blastocyst development and maternal-fetal cross talk. Cell Stem Cell 30(9), 1246-1261.e9.
| Crossref | Google Scholar | PubMed |

Yuan Y (2018) Capturing bovine pluripotency. Proceedings of the National Academy of Sciences of the United States of America 115(9), 1962-1963.
| Crossref | Google Scholar |

Zhang S, Chen T, Chen N, Gao D, Shi B, Kong S, West RC, Yuan Y, Zhi M, Wei Q, Xiang J, Mu H, Yue L, Lei X, Wang X, Zhong L, Liang H, Cao S, Belmonte JCI, Wang H, Han J (2019) Implantation initiation of self-assembled embryo-like structures generated using three types of mouse blastocyst-derived stem cells. Nature Communications 10(1), 496.
| Crossref | Google Scholar | PubMed |

Zhang P, Zhai X, Huang B, Sun S, Wang W, Zhang M (2023) Highly efficient generation of blastocyst-like structures from spliceosomes-repressed mouse totipotent blastomere-like cells. Science China Life Sciences 66(3), 423-435.
| Crossref | Google Scholar | PubMed |

Zhao L, Gao X, Zheng Y, Wang Z, Zhao G, Ren J, Zhang J, Wu J, Wu B, Chen Y, Sun W, Li Y, Su J, Ding Y, Gao Y, Liu M, Bai X, Sun L, Cao G, Tang F, Bao S, Liu P, Li X (2021) Establishment of bovine expanded potential stem cells. Proceedings of the National Academy of Sciences of the United States of America 118, e2018505118.
| Crossref | Google Scholar |

Zhao C, Reyes AP, Schell JP, Weltner J, Ortega NM, Zheng Y, Björklund ÅK, Baqué-Vidal L, Sokka J, Torokovic R, Cox B, Rossant J, Fu J, Petropoulos S, Lanner F (2024) A comprehensive human embryogenesis reference tool using single-cell RNA-sequencing data. BioRxiv [Preprint].
| Crossref | Google Scholar |

Zheng Y, Xue X, Shao Y, Wang S, Esfahani SN, Li Z, Muncie JM, Lakins JN, Weaver VM, Gumucio DL, Fu J (2019) Controlled modelling of human epiblast and amnion development using stem cells. Nature 573(7774), 421-425.
| Crossref | Google Scholar | PubMed |

Zheng Y, Yan RZ, Sun S, Kobayashi M, Xiang L, Yang R, Goedel A, Kang Y, Xue X, Esfahani SN, Liu Y, Resto Irizarry AM, Wu W, Li Y, Ji W, Niu Y, Chien KR, Li T, Shioda T, Fu J (2022) Single-cell analysis of embryoids reveals lineage diversification roadmaps of early human development. Cell Stem Cell 29(9), 1402-1419.e8.
| Crossref | Google Scholar |

Zhou F, Wang R, Yuan P, Ren Y, Mao Y, Li R, Lian Y, Li J, Wen L, Yan L, Qiao J, Tang F (2019) Reconstituting the transcriptome and DNA methylome landscapes of human implantation. Nature 572(7771), 660-664.
| Crossref | Google Scholar | PubMed |